Improvements are needed in mass spectrometry and more specifically improvements to an ionization source to allow analysis that is more sensitive and provide other analytical and operational advantages.
Mass spectrometer (MS) instruments analyze compounds and mixtures by measuring the mass-to-charge ratio (M/Z) of ionized molecules generated at a source. MS instruments vaporize and ionize a sample and determine the mass-to-charge ratio of the resulting ions. Quadrupole, time-of-flight (TOF) and ion trap are types of mass spectrometers.
An MS system generally consists of a chromatograph (gas or liquid) or alternate device to introduce an analyte for analysis; an ionization source with a chamber to produce ions from the analyte; a mass analyzer or filter to separate ions according to their mass-to-charge ratio; a detector to measure ion abundance; and an instrument control and data-handling system to produce a mass spectrum of the analyte.
In the operation of an MS instrument, an ionization source generates charged molecules for mass identification. Ionization sources useful in mass spectrometry include, for example electron impact (EI), chemical ionization (CI), negative chemical ionization (NID), fast ion or atom bombardment, field desorption, laser desorption, plasma desorption, thermospray, electrospray and inductively coupled plasma. A problem typically encountered with an EI ionization source has been that the mechanical components of a conventional EI ionization source use a magnetic or electrical field to focus ions to the filter or analyzing point. These mechanical components tend to be ignored, as the analyte is not analyzed in the source. However, it would be preferable to generate the charged molecules while maintaining inertness and mechanical integrity throughout the ion source.
A quadrupole consists of four conductive rods that with the proper application of radio frequency and direct current ramped energy fields create a tunable mass filter allowing only the ions of the selected mass-to-charge ratio to transit. Ions are injected on one side from the ion source and filtered by the rods. Those that meet the proper mass-top-charge ratio are allowed to pass and create a mass spectrum on a time axis.
A time-of-flight (TOF) MS instrument determines the mass-to-charge ratio of an ion by measuring the amount of time it takes a given ion to migrate from the ion source to the detector, under influence of electric fields. TOF MS instruments accelerate a pulsed ion beam across a nearly constant potential and measure the flight time of ions from their origination at the source to a detector. Since the kinetic energy per charge of an ion is nearly constant, heavier ions move more slowly and arrive at the detector later in time than lighter ions. Using the flight times of ions with known M/Z values, the TOF spectrometer is calibrated and the flight time of an unknown ion is converted into an M/Z value. TOF MS instruments have been primarily used with pulsed sources generating a discrete burst of ions. Examples of MS instruments with pulsed sources include plasma desorption MS instruments and secondary ionization MS instruments. Ionization methods include matrix assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI).
An ion trap MS instrument has a ring electrode and a pair of end cap electrodes, which form an ion trap region. The ion trap MS instrument operates with an electron impact (EI) ion source including an ionization step and a mass-analyzing step. In the ionization step, a sample in an ion trap region ionizes by collision with electrons, and resulting ions accumulate in the ion trap region. In the a mass analyzing step, the ion trap region consecutively ejects accumulated ions by radio frequency (RF) voltage scanning applied to the electrodes, and a detector detects the ejected ions.
Ionization sources operate in a similar manner. An analyte in gaseous or liquid form is introduced into the chamber containing the ionization source, and the ionization source partially ionizes the analyte. As previously mentioned, illustrative ionization sources useful in mass spectrometry include, for example: EI, CI, NID, fast ion or atom bombardment, field desorption, laser desorption, plasma desorption, thermospray, electrospray and inductively coupled plasma. Two accepted and widely used ionization sources to create ions in MS instruments are EI and CI ionization sources.
In an EI ionization source of a conventional MS instrument, introduction of an electron beam creates charged molecules. The EI source generally contains a heated filament to emit electrons that accelerate toward an anode and collide with gaseous analyte molecules introduced into the ionization chamber. The beam of emitted electrons focuses in the ionization chamber where the analyte is introduced. Typically, relatively high-energy electrons (of about 70 eV) collide with molecules of the subject analyte, producing ions with an efficiency of less than a few percent. These collisions produce primarily positive ions. Upon ionization, the molecules of a given substance fragment in predictable patterns. The resultant ions separate by their mass-to-charge ratio in the mass analyzer or filter and collect in the detector. EI is a direct process; energy transfers collisionally from electrons to analyte molecules. Total pressure within the EI ionization source is normally less than about 10−3 torr. The ions produced are extracted from the EI source with an applied electric field and generally do not collide with other molecules or surfaces from their formation in the EI source until their collection in the detector.
The surfaces of the analyte area or chamber containing the ionization source are highly susceptible to analyte absorption. Molecular interactions between the products of the introduced analyte and the surfaces of the chamber and the ionization source can distort the true quantity and quality of the presented analyte. Due to temperature, vacuum, and electrical considerations, metal surfaces (such as stainless steel) have typically been used for construction of the ionization source. It has long been desired to provide a greater degree of mechanical isolation between the charged ions of the analyte and the adsorptive surfaces of the chamber and the ionization source.
In all ion sources, it has not been thought necessary to prevent adsorption, degradation or decomposition of analyte ions or to prevent adverse reactions of gaseous ions on the surface of the sources. Any such secondary ions have not been thought to affect the intended measurement.
After formation of ions in the ionization source, five basic types of mass analyzers or filters are available for ion separation, including magnetic, electrostatic, time-of-flight, ion cyclotron resonance, quadrupole, and variations of the quadrupole. Typical detectors used in MS instruments are discrete and continuous dyanode electron multipliers.
Other workers have made efforts to address analyte degradation problems in an MS ionization chamber by substituting or modifying ionization chamber surfaces. For example, chromium or oxidized chromium surfaces in an analyte analyzing and ionizing apparatus, such as an ion trap or ionization chamber, have been used to prevent degradation or decomposition of an analyte in contact with those surfaces. An inert, inorganic, non-metallic insulator or semiconductor coating material on the ion trap or ionization chamber interior surfaces has been used to reduce adsorption, degradation or decomposition of an analyte in contact with the surface. Silicon coated steel has also been used in place of certified stainless steel with some reported improvement in results. Furthermore, coating the inner surface of the ionization with chamber materials known for corrosion resistance or inertness, such as nickel, rhodium, and the like, may retard degradation of some analytes.
Other attempts to prevent degradation problems involve treating the inner metal surfaces of the analytical apparatus with a passivating agent to mask or destroy active surface sites. For example, gas chromatographic injectors, chromatographic columns, transfer lines, and detectors have been treated with alkylchlorosilanes and other silylizing agents. Such treatments have had some success in deactivating metal surfaces and preventing degradation. Unfortunately, the materials used for such treatments have sufficiently high vapor pressure, produce gas phase organic materials within the ionization chamber volume, and ionize along with the analyte, producing a high chemical background in the mass spectrum. MS instruments using such ionization chambers give variable results and do not completely prevent analyte degradation over time.
In addition to metal surface degradation problems just described, currently available ionization sources tend to corrode or degrade over extended periods and require cleaning and reconditioning for continued use. Often cleaning procedures include aggressive mechanical abrading procedures that can stress, deform or even break affected portions of the ionization source. Such procedures result in extended equipment downtime and often result in breakage of the involved parts, requiring costly replacement.